title: A role for fibroblast growth factor 19 and bile acids in diabetes remission after Roux-en-Y gastric bypass.
abstract: OBJECTIVE
  Roux-en-Y gastric bypass (RYGB) in humans can remit type 2 diabetes, but the operative mechanism is not completely understood. In mice, fibroblast growth factor (FGF) 15 (FGF19 in humans) regulates hepatic bile acid (BA) production and can also resolve diabetes. In this study, we tested the hypothesis that the FGF19-BA pathway plays a role in the remission of human diabetes after RYGB surgery.
  
  
  METHODS
  Cohorts of diabetic and nondiabetic individuals of various body weights were used. In addition, RYGB patients without diabetes (No-Diabetes), RYGB patients with diabetes who experienced remission for at least 12 months after surgery (Diabetes-R), and RYGB patients with diabetes who did not go into remission after surgery (Diabetes-NoR) were studied. Circulating FGF19 and BA levels, hepatic glycogen content, and expression levels of genes regulating the FGF19-BA pathway were compared among these groups of patients using pre- and postoperative serum samples and intraoperative liver biopsies.
  
  
  RESULTS
  Preoperatively, patients with diabetes had lower FGF19 and higher BA levels than nondiabetic patients, irrespective of body weight. In diabetic patients undergoing RYGB, lower FGF19 levels were significantly correlated with increased hepatic expression of the cholesterol 7alpha-hydroxylase 1 (CYP7A1) gene, which modulates BA production. Following RYGB surgery, however, FGF19 and BA levels (particularly cholic and deoxycholic acids) exhibited larger increases in Diabetic-R patients compared with nondiabetic and Diabetic-NoR patients.
  
  
  CONCLUSIONS
  Taken together, the baseline and postoperative data implicate the FGF19-CYP7A1-BA pathway in the etiology and remission of type 2 diabetes following RYGB surgery.
authors.affiliation: Weis Center for Research, Geisinger Clinic, Danville, Pennsylvania, USA.
authors.forename: Glenn S
authors.initials: GS
authors.lastname: Gerhard
authors.forename: Amanda M
authors.initials: AM
authors.lastname: Styer
authors.forename: G Craig
authors.initials: GC
authors.lastname: Wood
authors.forename: Stephen L
authors.initials: SL
authors.lastname: Roesch
authors.forename: Anthony T
authors.initials: AT
authors.lastname: Petrick
authors.forename: Jon
authors.initials: J
authors.lastname: Gabrielsen
authors.forename: William E
authors.initials: WE
authors.lastname: Strodel
authors.forename: Christopher D
authors.initials: CD
authors.lastname: Still
authors.forename: George
authors.initials: G
authors.lastname: Argyropoulos
mesh_terms: D000368:Aged; D001647:Bile Acids and Salts / Q000097:blood*; D002790:Cholesterol 7-alpha-Hydroxylase / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000097:blood* / Q000209:etiology* / Q000378:metabolism; D005260:Female; D005346:Fibroblast Growth Factors / Q000097:blood* / Q000378:metabolism; D015390:Gastric Bypass / Q000009:adverse effects*; D006801:Humans; D008297:Male; D008875:Middle Aged
chemical_list: D001647:Bile Acids and Salts; C117476:FGF19 protein, human; D005346:Fibroblast Growth Factors; C553219:CYP7A1 protein, human; D002790:Cholesterol 7-alpha-Hydroxylase